bevacizumab, cetuximab, and cisplatin with imrt (intensity-modulated radiation therapy) for patients with stage iii/iv head and neck squamous cell carcinoma

Conditions: Head and Neck Cancer

Summary: the purpose of this study is to determine the effectiveness of treatment with bevacizumab + cisplatin + cetuximab + imrt. the doctor wishes to monitor patients for 2 years after the completion of study treatment to determine if they are cancer-free during that time. they also want to evaluate the side effects that patients experience with this treatment regimen.


Eligibility criteria:
inclusion criteria: * stage iii/iv hnscc without distant metastasis. patients with stage ii squamous cell carcinoma of the hypopharynx will also be eligible * adequate renal function, with serum creatinine ≤ 1.5 mg/dl. patients with serum creatinine \> 1.5 mg/dl may be eligible if calculated creatinine clearance \> or = to 55 ml/min by cockcroft and gault equation (or 24-hour urine collection). * age \> or = to 18 years. * karnofsky performance status \> or = to 70% * adequate bone marrow function: absolute neutrophil count \> or = to 1,500/ platelets \> or = to 100,000/ul, hemoglobin \> or = to 9 gm/dl * adequate hepatic function: total bilirubin ≤ 1.5 x uln (patients with gilbert's syndrome as the cause of hyperbilirubinemia may be eligible if total bilirubin ≤ 2.5 x uln), aspartate aminotransferase (ast) ≤ 2.5 x uln, alanine aminotransferase (alt) ≤ 2.5 x uln, alkaline phosphatase ≤ 2.5 x uln. * men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter. * patients must have ability to understand and the willingness to sign a written informed consent document. exclusion criteria: * prior radiation therapy for hnscc * prior treatment of hnscc with bevacizumab or other agents specifically targeting vegf * prior treatment of hnscc with cetuximab or other agents specifically targeting egfr * other active malignancy, other than indolent malignancies, which the investigator determines are unlikely to interfere with treatment or efficacy analysis. for example, patients with non-melanoma skin cancer, in situ carcinoma of the cervix, or prostate cancer within the no current biochemical (psa) or radiologic evidence of disease may enroll. * patients with nasopharyngeal carcinoma * patients who will receive amifostine as part of the radiation treatment plan * patients with skin breakdown/ulceration (ctcae version 3.0, grade 2 or higher). * patients with hearing loss requiring hearing aid or intervention (i.e. interfering in a clinically significant way with activities of daily living). * patients with multifocal peripheral sensory alterations or paresthesias (including tingling) interfering with function, per patient report (example: activities of daily living). * any prior documented history of transient ischemic attack (tia) or cerebrovascular accident (cva) * history of unstable angina or myocardial infarction (mi) within the last year. * urine protein: creatinine (upc) ratio \> or = to 1.0 at screening. a random urine sample is collected. total protein (mg/dl) and spot creatinine (mg/dl) are ordered for this sample. the upc ratio is calculated from the results of these tests. * international normalized ratio (inr) \> 1.5 or activated partial thromboplastin time (aptt) \> 1.5 x upper limits of normal (uln) * current use of warfarin, current use of heparin or low-molecular weight heparin, chronic daily treatment with aspirin (\> 325 mg/day) or nonsteroidal anti-inflammatory medications known to inhibit platelet function. * patients with gross hemoptysis or hematemesis (defined as bright red blood of 1 teaspoon of more) within 28 days prior to day 0 protocol treatment will be excluded from this trial. patients with incidental blood mixed with phlegm are not excluded. * esophageal varices, non-healing ulcer, wound, or bone fracture are exclusion criteria. however, patients with skin breakdown overlying malignant neck lymphadenopathy may be eligible, at the discretion of the investigator. * anatomic lesion that increases the risk of serious hemorrhage, such as encasement or invasion of major blood vessels by primary tumor and/or by involved lymph nodes * blood pressure of \> 150/100 mmhg * new york heart association (nyha) grade ii or greater congestive heart failure. * clinically significant peripheral vascular disease * history of bleeding diathesis or hemorrhagic disorder, or coagulopathy. * major surgical procedure or significant traumatic injury within 28 days prior to treatment with bevacizumab * core biopsy within 7 days prior to treatment with bevacizumab. * minor surgical procedures such as fine needle aspirations or placement of percutaneous gastrostomy tube (peg) less than 7 days prior to treatment with bevacizumab * history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior enrollment. * inability to comply with study and/or follow-up procedures * women who are pregnant or lactating

Keywords: bevacizumab cisplatin cetuximab radiation therapy phase ii 09-083